Long-term evaluation of the safety and efficacy of recombinant human pentraxin-2 : an open-label extension study

• Published in: Respiratory research Vol. 23; no. 1
• Main Authors: Raghu, Ganesh, Hamblin, Mark J, Brown, A. Whitney, Golden, Jeffrey A, Ho, Lawrence A, Wijsenbeek, Marlies S, Vasakova, Ma, Pesci, Alberto, Antin-Ozerkis, Danielle E, Meyer, Keith C, Kreuter, Michael, Burgess, Tracy, Kamath, Nikhil, Donaldson, Francis, Richeldi, Luca
• Format: Journal Article
• Language: English
• Published: BioMed Central Ltd 21-05-2022
• Subjects: Care and treatment; Genetic aspects; Glycoproteins; Health aspects; Patient outcomes; Pulmonary fibrosis; Italy
• ISSN: 1465-9921
• DOI: 10.1186/s12931-022-02047-0

Background Recombinant human pentraxin-2 (rhPTX-2) significantly decreased decline in percent predicted forced vital capacity (FVC) and stabilized 6-min walk distance (6MWD) in patients with idiopathic pulmonary fibrosis (IPF) during the 28-week, placebo-controlled, randomized period of the Phase II PRM-151-202 study. Interim (76-week) data from the open-label extension (OLE) demonstrated sustained safety and efficacy with rhPTX-2 treatment. Here, we present the entire long-term OLE safety and efficacy data to 128 weeks. Methods Patients who completed the randomized PRM-151-202 study period were eligible for the OLE, during which all patients received rhPTX-2, having started rhPTX-2 (i.e., crossed from placebo) or continued rhPTX-2 after Week 28. rhPTX-2 was administered in 28-week cycles, with 10 mg/kg intravenous infusions (60 min) on Days 1, 3, and 5 in the first week of each cycle, then one infusion every 4 weeks up to Week 128. The OLE primary objective was to assess the long-term safety and tolerability of rhPTX-2. Other outcomes included FVC, 6MWD, and patient-reported outcomes (descriptive analysis). Results All 111 patients who completed the randomized period entered the OLE (n = 37 started rhPTX-2; n = 74 continued rhPTX-2); 57 (51.4%) completed to Week 128. The treatment-emergent adverse event (TEAE) profile was consistent with the randomized period, with the majority of TEAEs graded mild or moderate. Serious TEAEs occurred in 47 patients (42.3%), most frequently IPF (n = 11; 9.9%), pneumonia (n = 7; 6.3%), and acute respiratory failure (n = 3; 2.7%). Three patients underwent lung transplantation. Most serious TEAEs (and all 14 fatal events) were considered unrelated to rhPTX-2 treatment. For patients starting vs continuing rhPTX-2, mean (95% confidence interval) changes from baseline to Week 128 were, respectively, - 6.2% (- 7.7; - 4.6) and - 5.7% (- 8.0; - 3.3) for percent predicted FVC and - 36.3 m (- 65.8; - 6.9) and - 28.9 m (- 54.3; - 3.6) for 6MWD; however, conclusions were limited by patient numbers at Week 128. Conclusions Long-term treatment (up to 128 weeks) with rhPTX-2 was well tolerated in patients with IPF, with no new safety signals emerging in the OLE. The limited efficacy data over 128 weeks may suggest a trend towards a treatment effect. Trial registration NCT02550873; EudraCT 2014-004782-24. Keywords: Recombinant human pentraxin-2 (rhPTX-2), Idiopathic pulmonary fibrosis (IPF), Long-term, Safety, Open-label extension, Forced vital capacity (FVC), 6-minute walk distance (6MWD)